Unique somatic variants in DNA from urine exosomes of individuals with bladder cancer.
Unique somatic variants in DNA from urine exosomes of individuals with bladder cancer.
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DOI：
10.1016/j.omtm.2021.05.010
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发表时间：
2021-09-10
期刊：
影响因子：
--
通讯作者：
Kalluri R
中科院分区：
文献类型：
--
作者：
Zhou X;Kurywchak P;Wolf-Dennen K;Che SPY;Sulakhe D;D'Souza M;Xie B;Maltsev N;Gilliam TC;Wu CC;McAndrews KM;LeBleu VS;McConkey DJ;Volpert OV;Pretzsch SM;Czerniak BA;Dinney CP;Kalluri R
膀胱癌（BC）是一种以高复发率为特征的异质性疾病，通过膀胱镜检查进行诊断和监测。基于活检的准确临床分期仍然是一个挑战，迫切需要额外的客观诊断工具。我们使用外泌体 DNA (exoDNA) 作为分析物来检查与癌症相关的突变，并比较了 BC 患者尿液和血清中的外泌体 DNA 的诊断效用。与健康个体的尿液外泌体相比，BC 患者的尿液外泌体含有大量 DNA。对来自匹配的尿液和血清外泌体、膀胱肿瘤和正常组织（外周血单核细胞）的 DNA 进行全外显子组测序，鉴定出 BC 中频繁突变基因的外显子和 3'UTR 变异，这些变异可在尿液外泌体 DNA 和匹配的肿瘤样本中检测到。进一步的分析发现了驱动基因中的体细胞变异，这是尿液外切 DNA 所特有的，可能是由于 BC 固有的肿瘤内异质性，而这种异质性在随机小活检中并未得到充分体现。在基因组的非翻译部分中也发现了多种变异，例如 KRAS 基因的 microRNA (miRNA) 结合区域。基因网络分析表明，外泌体 DNA 与 BC 外泌体中的癌症、炎症和免疫相关。我们的研究结果表明，外切 DNA 作为一种客观、非侵入性策略可用于识别 BC 的新型生物标志物和靶点。尿液外泌体衍生的 DNA 可用作检测膀胱癌的客观且新颖的生物标志物。
Bladder cancer (BC), a heterogeneous disease characterized by high recurrence rates, is diagnosed and monitored by cystoscopy. Accurate clinical staging based on biopsy remains a challenge, and additional, objective diagnostic tools are needed urgently. We used exosomal DNA (exoDNA) as an analyte to examine cancer-associated mutations and compared the diagnostic utility of exoDNA from urine and serum of individuals with BC. In contrast to urine exosomes from healthy individuals, urine exosomes from individuals with BC contained significant amounts of DNA. Whole-exome sequencing of DNA from matched urine and serum exosomes, bladder tumors, and normal tissue (peripheral blood mononuclear cells) identified exonic and 3′ UTR variants in frequently mutated genes in BC, detectable in urine exoDNA and matched tumor samples. Further analyses identified somatic variants in driver genes, unique to urine exoDNA, possibly because of the inherent intra-tumoral heterogeneity of BC, which is not fully represented in random small biopsies. Multiple variants were also found in untranslated portions of the genome, such as microRNA (miRNA)-binding regions of the KRAS gene. Gene network analyses revealed that exoDNA is associated with cancer, inflammation, and immunity in BC exosomes. Our findings show utility of exoDNA as an objective, non-invasive strategy to identify novel biomarkers and targets for BC. Urine exosome-derived DNA can be used as an objective and novel biomarker for detection of bladder cancer.
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影响因子：
11
作者：
Devanna P;Chen XS;Ho J;Gajewski D;Smith SD;Gialluisi A;Francks C;Fisher SE;Newbury DF;Vernes SC
通讯作者：
Vernes SC
DOI：
10.1007/s00018-014-1764-3
发表时间：
2015-02
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Brinton LT;Sloane HS;Kester M;Kelly KA
通讯作者：
Kelly KA
影响因子：
11.2
作者：
Byun, Hyang-Min;Wong, Hui-Lee;Yang, Allen S.
通讯作者：
Yang, Allen S.
影响因子：
6.2
作者：
Charlton, Mary E.;Adamo, Margaret (Peggy);Sun, Leon;Deorah, Sundeep
通讯作者：
Deorah, Sundeep
影响因子：
3.7
作者：
Borgström E;Paterlini M;Mold JE;Frisen J;Lundeberg J
通讯作者：
Lundeberg J